GB795459A - Isoxazolidone derivatives and a process for the manufacture thereof - Google Patents

Abstract

The invention comprises DL-5-alkyl-4-aminoisoxazolidones-(3), and the preparation thereof and of 4-aminoisoxazolidone-(3) itself by esterifying an a -amino-b -hydroxypropiohydroxamic acid derivative of the general formula: <FORM:0795459/IV (b)/1> (wherein R represents hydrogen or an alkyl group, R1 represents an aralkyl group and X represents benzyloxycarbonyl) with an aromatic or aliphatic sulphonic acid halide, hydrogenolysing the resulting ester and treating the resulting hydroxamic acid with a basic agent. The esterification step is advantageously carried out in the presence of a tertiary base with or without an inert solvent, and the hydrogenolysis step by means of catalytically activated hydrogen or an alkali-metal in liquid ammonia, whilst the basic agent in the third step may be an alkali metal alkoxide, hydroxide or carbonate, gaseous ammonia, an organic base or a basic exchange-resin, suitably in aqueous or alcoholic solution. The second and third steps may be combined by hydrogenating the esterification mixture in the presence of an alkali metal alkoxide in alcoholic solution or, when using an alkali metal in liquid ammonia in the second step, the liquid ammonia may be evaporated and water added to form with the remaining alkali metal the hydroxide thereof which acts as the basic agent. In examples: (1) DL - a - benzyloxycarbonylamino - b - hydroxypropiohydroxamic acid O-benzyl ether is esterified with p-toluene-sulphonic acid chloride and pyridine, the product is suspended in ethanol and hydrogenated in the presence of palladium, after which a solution of sodium methoxide in ethanol is added and the mixture warmed to produce 4-aminoisoxazolidone-(3); alternatively the sodium methoxide solution is added to the esterification product and the hydrogenolysis is effected in the presence thereof, or the esterification product is dissolved in liquid ammonia, sodium is added until a blue coloration persists, the ammonia is then allowed to evaporate and the residue dissolved in water, or hydrogenation of the esterification product is effected in aqueous alcoholic hydrobromic acid solution, and a stream of dry NH3 is then passed in; (2) DL-a -benzyloxycarbonylamino - b - hydroxybutyro-hydroxamic acid O-benzyl ether is esterified with methanesulphonic acid chloride and pyridine and the product is subjected to the last of the four alternative treatments in (1), giving DL-4-amino-5-methylisoxazolidone-(3). Specification 795,458 is referred to.